Neuropathology of Parkinson’s disease

John E. Duda, Dennis W Dickson

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The past few decades have witnessed major advances in our understanding of the pathophysiology of parkinsonism, including the recognition of MPTP-induced parkinsonism (Langston et al. 1983), the discovery of numerous genes responsible for rare Mendelian forms of parkinsonism (Hardy et al. 2009), and the identification of α-synuclein as the primary component of Lewy bodies (LBs) (Spillantini et al. 1997), the hallmark histopathologic lesion of Parkinson’s disease (PD) (Shults 2006). These advances have led to the development of both cellular and animal models that recapitulate key features of PD. These models hold potential for identifying mechanisms of nigrostriatal degeneration and for development of disease-modifying treatments for PD. They have been used in the development of novel neuroprotective strategies, but so far, these discoveries have not successfully translated into clinical use. While the reasons for these failures of translation are debatable (Ahlskog 2007, Waldmeier et al. 2006), it is possible that the pathophysiologic mechanisms of genetic and acute intoxication forms of parkinsonism do not apply to PD. This seems particularly likely for causes of parkinsonism that do not involve the formation of aggregates of insoluble α-synuclein (Hasegawa et al. 2009, Wszolek et al. 2004). Most of the existing models of PD have been developed in young animals, and more emphasis on understanding the changes that occur in the aging nervous system may be necessary. There are probably numerous ways that highly vulnerable mesencephalic dopaminergic neurons can be damaged, not all of which are relevant to PD. Indeed, most of the atypical parkinsonian disorders that also produce nigral degeneration, including progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy involve disease mechanisms, such as accumulation of abnormal tau protein in neurons and glia (Ballatore et al. 2007) or primary α-synuclein pathology in glial cells (Wenning et al. 2008) that may not be relevant to PD. For these reasons, this chapter will focus on the neuropathology of the most common pathologic substrate of parkinsonism, LB disease.

Original languageEnglish (US)
Title of host publicationParkinson's Disease, Second Edition
PublisherCRC Press
Pages493-506
Number of pages14
ISBN (Electronic)9781439807156
ISBN (Print)9781439807149
DOIs
StatePublished - Jan 1 2012

Fingerprint

Parkinsonian Disorders
Parkinson Disease
Synucleins
Neuroglia
MPTP Poisoning
Progressive Supranuclear Palsy
Multiple System Atrophy
Lewy Bodies
Lewy Body Disease
tau Proteins
Dopaminergic Neurons
Genetic Association Studies
Substantia Nigra
Neuropathology
Nervous System
Animal Models
Pathology
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Duda, J. E., & Dickson, D. W. (2012). Neuropathology of Parkinson’s disease. In Parkinson's Disease, Second Edition (pp. 493-506). CRC Press. https://doi.org/10.1201/b12948

Neuropathology of Parkinson’s disease. / Duda, John E.; Dickson, Dennis W.

Parkinson's Disease, Second Edition. CRC Press, 2012. p. 493-506.

Research output: Chapter in Book/Report/Conference proceedingChapter

Duda, JE & Dickson, DW 2012, Neuropathology of Parkinson’s disease. in Parkinson's Disease, Second Edition. CRC Press, pp. 493-506. https://doi.org/10.1201/b12948
Duda JE, Dickson DW. Neuropathology of Parkinson’s disease. In Parkinson's Disease, Second Edition. CRC Press. 2012. p. 493-506 https://doi.org/10.1201/b12948
Duda, John E. ; Dickson, Dennis W. / Neuropathology of Parkinson’s disease. Parkinson's Disease, Second Edition. CRC Press, 2012. pp. 493-506
@inbook{f6f75f178a444f01a84cc494d6ef069a,
title = "Neuropathology of Parkinson’s disease",
abstract = "The past few decades have witnessed major advances in our understanding of the pathophysiology of parkinsonism, including the recognition of MPTP-induced parkinsonism (Langston et al. 1983), the discovery of numerous genes responsible for rare Mendelian forms of parkinsonism (Hardy et al. 2009), and the identification of α-synuclein as the primary component of Lewy bodies (LBs) (Spillantini et al. 1997), the hallmark histopathologic lesion of Parkinson’s disease (PD) (Shults 2006). These advances have led to the development of both cellular and animal models that recapitulate key features of PD. These models hold potential for identifying mechanisms of nigrostriatal degeneration and for development of disease-modifying treatments for PD. They have been used in the development of novel neuroprotective strategies, but so far, these discoveries have not successfully translated into clinical use. While the reasons for these failures of translation are debatable (Ahlskog 2007, Waldmeier et al. 2006), it is possible that the pathophysiologic mechanisms of genetic and acute intoxication forms of parkinsonism do not apply to PD. This seems particularly likely for causes of parkinsonism that do not involve the formation of aggregates of insoluble α-synuclein (Hasegawa et al. 2009, Wszolek et al. 2004). Most of the existing models of PD have been developed in young animals, and more emphasis on understanding the changes that occur in the aging nervous system may be necessary. There are probably numerous ways that highly vulnerable mesencephalic dopaminergic neurons can be damaged, not all of which are relevant to PD. Indeed, most of the atypical parkinsonian disorders that also produce nigral degeneration, including progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy involve disease mechanisms, such as accumulation of abnormal tau protein in neurons and glia (Ballatore et al. 2007) or primary α-synuclein pathology in glial cells (Wenning et al. 2008) that may not be relevant to PD. For these reasons, this chapter will focus on the neuropathology of the most common pathologic substrate of parkinsonism, LB disease.",
author = "Duda, {John E.} and Dickson, {Dennis W}",
year = "2012",
month = "1",
day = "1",
doi = "10.1201/b12948",
language = "English (US)",
isbn = "9781439807149",
pages = "493--506",
booktitle = "Parkinson's Disease, Second Edition",
publisher = "CRC Press",

}

TY - CHAP

T1 - Neuropathology of Parkinson’s disease

AU - Duda, John E.

AU - Dickson, Dennis W

PY - 2012/1/1

Y1 - 2012/1/1

N2 - The past few decades have witnessed major advances in our understanding of the pathophysiology of parkinsonism, including the recognition of MPTP-induced parkinsonism (Langston et al. 1983), the discovery of numerous genes responsible for rare Mendelian forms of parkinsonism (Hardy et al. 2009), and the identification of α-synuclein as the primary component of Lewy bodies (LBs) (Spillantini et al. 1997), the hallmark histopathologic lesion of Parkinson’s disease (PD) (Shults 2006). These advances have led to the development of both cellular and animal models that recapitulate key features of PD. These models hold potential for identifying mechanisms of nigrostriatal degeneration and for development of disease-modifying treatments for PD. They have been used in the development of novel neuroprotective strategies, but so far, these discoveries have not successfully translated into clinical use. While the reasons for these failures of translation are debatable (Ahlskog 2007, Waldmeier et al. 2006), it is possible that the pathophysiologic mechanisms of genetic and acute intoxication forms of parkinsonism do not apply to PD. This seems particularly likely for causes of parkinsonism that do not involve the formation of aggregates of insoluble α-synuclein (Hasegawa et al. 2009, Wszolek et al. 2004). Most of the existing models of PD have been developed in young animals, and more emphasis on understanding the changes that occur in the aging nervous system may be necessary. There are probably numerous ways that highly vulnerable mesencephalic dopaminergic neurons can be damaged, not all of which are relevant to PD. Indeed, most of the atypical parkinsonian disorders that also produce nigral degeneration, including progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy involve disease mechanisms, such as accumulation of abnormal tau protein in neurons and glia (Ballatore et al. 2007) or primary α-synuclein pathology in glial cells (Wenning et al. 2008) that may not be relevant to PD. For these reasons, this chapter will focus on the neuropathology of the most common pathologic substrate of parkinsonism, LB disease.

AB - The past few decades have witnessed major advances in our understanding of the pathophysiology of parkinsonism, including the recognition of MPTP-induced parkinsonism (Langston et al. 1983), the discovery of numerous genes responsible for rare Mendelian forms of parkinsonism (Hardy et al. 2009), and the identification of α-synuclein as the primary component of Lewy bodies (LBs) (Spillantini et al. 1997), the hallmark histopathologic lesion of Parkinson’s disease (PD) (Shults 2006). These advances have led to the development of both cellular and animal models that recapitulate key features of PD. These models hold potential for identifying mechanisms of nigrostriatal degeneration and for development of disease-modifying treatments for PD. They have been used in the development of novel neuroprotective strategies, but so far, these discoveries have not successfully translated into clinical use. While the reasons for these failures of translation are debatable (Ahlskog 2007, Waldmeier et al. 2006), it is possible that the pathophysiologic mechanisms of genetic and acute intoxication forms of parkinsonism do not apply to PD. This seems particularly likely for causes of parkinsonism that do not involve the formation of aggregates of insoluble α-synuclein (Hasegawa et al. 2009, Wszolek et al. 2004). Most of the existing models of PD have been developed in young animals, and more emphasis on understanding the changes that occur in the aging nervous system may be necessary. There are probably numerous ways that highly vulnerable mesencephalic dopaminergic neurons can be damaged, not all of which are relevant to PD. Indeed, most of the atypical parkinsonian disorders that also produce nigral degeneration, including progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy involve disease mechanisms, such as accumulation of abnormal tau protein in neurons and glia (Ballatore et al. 2007) or primary α-synuclein pathology in glial cells (Wenning et al. 2008) that may not be relevant to PD. For these reasons, this chapter will focus on the neuropathology of the most common pathologic substrate of parkinsonism, LB disease.

UR - http://www.scopus.com/inward/record.url?scp=85055847849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85055847849&partnerID=8YFLogxK

U2 - 10.1201/b12948

DO - 10.1201/b12948

M3 - Chapter

SN - 9781439807149

SP - 493

EP - 506

BT - Parkinson's Disease, Second Edition

PB - CRC Press

ER -